8K88

Structure of procaryotic Ago

Summary for 8K88

• Entry DOI: 10.2210/pdb8k88/pdb
• EMDB information: 36947
• Descriptor: DNA (41-mer), DNA/RNA (21-mer), Piwi domain protein, ... (5 entities in total)
• Functional Keywords: ago, dna/rna, dna binding protein, cell invasion, dna-rna-cell invasion complex, dna/rna/cell invasion
• Biological source: Geobacter sulfurreducens; More
• Total number of polymer chains: 4
• Total formula weight: 139196.88

Authors

Gao, X.,Sun, D.,Cui, S.,Wang, Y. (deposition date: 2023-07-29, release date: 2024-07-03, Last modification date: 2024-09-18)

Primary citation

Sun, D.,Zhu, K.,Wang, L.,Mu, Z.,Wu, K.,Hua, L.,Qin, B.,Gao, X.,Wang, Y.,Cui, S.
Nucleic acid-induced NADase activation of a short Sir2-associated prokaryotic Argonaute system.
Cell Rep, 43:114391-114391, 2024

PubMed Abstract: Inhibition of nucleic acid targets is mediated by Argonaute (Ago) proteins guided by RNA or DNA. Although the mechanisms underpinning the functions of eukaryotic and "long" prokaryotic Ago proteins (pAgos) are well understood, those for short pAgos remain enigmatic. Here, we determine two cryoelectron microscopy structures of short pAgos in association with the NADase-domain-containing protein Sir2-APAZ from Geobacter sulfurreducens (GsSir2/Ago): the guide RNA-target DNA-loaded GsSir2/Ago quaternary complex (2.58 Å) and the dimer of the quaternary complex (2.93Å). These structures show that the nucleic acid binding causes profound conformational changes that result in disorder or partial dissociation of the Sir2 domain, suggesting that it adopts a NADase-active conformation. Subsequently, two RNA-/DNA-loaded GsSir2/Ago complexes form a dimer through their MID domains, further enhancing NADase activity through synergistic effects. The findings provide a structural basis for short-pAgo-mediated defense against invading nucleic acids.

PubMed: 38923459
DOI: 10.1016/j.celrep.2024.114391

Experimental method

ELECTRON MICROSCOPY (2.6 Å)